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Annual Report Year 2

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Tetracycline Use and Bacterial Resistance

Antibiotics save lives; this fact is not in dispute.

Recently, though, their popularity among patients and caregivers has far exceeded their rational use against infection. A primary danger with the inappropriate use of these drugs is that bacteria and other organisms that cause infection can become resistant to the drugs.

Prescribing antibiotics to treat such conditions as upper respiratory tract infections, acute bronchitis, and acne, for example, might predispose patients to developing bacteria that will resist antibiotic treatment in the future. Indeed, many strains of certain bacteria now are resistant to all but one antibiotic drug, and strains of at least three others do not respond to treatment with any known antibiotic.

The costs of resistance are high, in both financial and human terms. Estimates range from $75 million to $7.5 billion per year for the financial costs of resistant infections. In addition, the Centers for Disease Control and Prevention (CDC) estimate that drug-resistant infections carry at least twice the risk of serious illness and new or prolonged hospitalization compared with infections susceptible to drugs.

The University of Pennsylvania (UPenn) CERTs is conducting a series of studies intended to make the use of these drugs more rational. As an example, one study is assessing the possible link between long-term tetracycline use for acne and the development of both antibiotic resistance and infections. Dr. David Margolis, a dermatologist and pharmacoepidemiologist, is leading the efforts at UPenn.

"Patients with acne often take oral antibiotics for many years," notes Margolis, "but the effect that the antibiotics may have on the health of these individuals or their families is not fully known. The current study is a first step in exploring this."

People with acne generally are treated with topical or oral medications. Tetracycline is the most commonly prescribed oral treatment, and topical agents often include tetracyclines as well. The oral antibiotics, though, may be more likely to result in bacterial colonization, especially of resistant bacteria, and possibly even infections.

The goal of the UPenn study, then, is to see whether the long-term use of oral tetracycline for acne will affect the presence and drug resistance of bacteria, in the throat specifically.

Dr. Margolis and colleagues are recruiting patients with acne from the outpatient dermatology clinic at the Hospital of the University of Pennsylvania. The patients must have been taking an oral tetracycline for at least 3 months before enrollment. The comparison group consists of people with acne who have not used oral tetracyclines for at least 6 months before enrollment in the study.

All study subjects have throat cultures taken, to measure the presence of two bacteria-Staphylococcus aureus and Streptococcus pyogenes-in the throat. If one or both of the bacteria is present, further tests are conducted to assess the resistance to tetracyclines.

So far, 44 patients have been recruited, of whom 34% were using an oral tetracycline. Of the people taking tetracycline, 5 of 13 had S. pyogenes present in the throat, 4 of 5 cases of which were resistant to tetracycline (table 1). Five of 12 patients taking tetracycline also showed S. aureus in the throat, 1 of 4 cases of which were resistant to tetracycline.

Among the control group, S. pyogenes was present in only 6 of 28 people, and only 1 case was resistant. For S. aureus, only 7 of 30 patients had the bacteria present in the throat, and 3 cases were resistant to tetracycline.

Additional subjects are still being enrolled, and information about infections of the upper respiratory tract must still be analyzed.

Follow-up projects will include a longitudinal assessment of the bacteria in the upper respiratory tract and the resulting propensity for infection in this area among acne patients, as well as a similar evaluation of people in close contact with acne patients.

This sequence of projects should contribute greatly to the UPenn CERTs overall goal of optimizing the risk/benefit balance in the use of antibiotics.

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